Immunomodulation by galectin-9: Distinct role in T cell populations, current therapeutic avenues and future potential
Eva M Gossink, Paul J. Coffer, Alessandro Cutilli, Caroline A. Lindemans
Abstract
• Galectin-9 (Gal-9) is emerging as a biomarker in multiple inflammatory conditions. • Differential roles are observed for Gal-9 in malignant and non-malignant diseases. • Gal-9 effects are context-dependent and dependent on the T cell subset involved. • Targeting Gal-9 could have both immune activating and suppressive effects. • The dual effect makes Gal-9 a complex immunotherapeutic target. Galectins, glycan-binding proteins, have been identified as critical regulators of the immune system. Recently, Galectin-9 (Gal-9) has emerged as biomarker that correlates with disease severity in a range of inflammatory conditions. However, Gal-9 has highly different roles in the context of immunoregulation, with the potential to either stimulate or suppress the immune response. Neutralizing antibodies targeting Gal-9 have been developed and are in early test phase investigating their therapeutic potential in cancer. Despite ongoing research, the mechanisms behind Gal-9 action remain not fully understood, and extrapolating the implications of targeting this molecule from previous studies is challenging. Here, we examine the pleiotropic function of Gal-9 focusing on conventional T lymphocytes, providing a current overview of its immunostimulatory and immunosuppressive roles. In particular, we highlight that Gal-9 differentially regulates immune responses depending on the context. Considering this complexity, further investigation of Gal-9′s intricate biology is necessary to define therapeutic strategies in immune disorders and cancer treatment aimed at inducing or inhibiting Gal-9 signaling.